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US 2025/0122182 A1Published application
MYST Inhibitors
AssigneeIsosterix, Inc.
InventorsRoopa Rai, Anjali Pandey, Leslie J. Holsinger
Life of this patent
Estimating the term…
Abstract
Provided herein are compounds that are MYST inhibitors, and pharmaceutically acceptable derivatives thereof. Also provided are pharmaceutical compositions containing the compounds and methods of using the compounds for treating a subject with a hyperproliferative disease including cancer.
Claims33
A compound of Formula I:
- or a pharmaceutically acceptable derivative thereof, wherein:
- a is 0-2;
- R1 and R2 are selected from (i) or (ii):
- (i) R1 is H, alkyl, haloalkyl or halo;
- and R2 is alkyl, cycloalkyl or haloalkyl, or
- (ii) R1 and R2 together form alkylene;
- R3 is —O—(CH2)b—R8;
- b is 1-4;
- R8 is H, CN, OH, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, NR9R10, C(O)R11, C(═NH)(R12) or C(═N—O—R9)(R12);
- R9 and R10 are each independently H, alkyl or C(O)R13;
- where R13 is alkyl, alkoxy or NR14R15;
- R11 is hydroxy, alkyl, alkoxy or NR14R15;
- R12 is alkyl or NR14R15;
- R14 and R15 are each independently H, OH, alkoxy or alkyl, or together with the nitrogen atom to which they are attached form heterocyclyl;
- R4 is H or alkoxy;
- Z1, Z2 and Z3 are selected from (i), (ii) or (iii):
- (i) Z1 is N, one of Z2 and Z3 is C and the other of Z2 and Z3 is N,
- (ii) Z1 is NH or O, and Z2 and Z3 are C, or
- (iii) Z1 is CH, one of Z2 and Z3 is C and the other of Z2 and Z3 is N;
- Z4 is CR16;
- Z5 is CR5;
- Z6 is N or CH;
- R5 and R16 together form alkylene or heteroalkylene;
- X is O, S(O)x or CH2, where x is 0-2;
- Het and R6 are selected from (i) or (ii):
- (i) Het is a 5- or 6-membered heteroaryl, and R6 is H, alkyl or haloalkyl, or
- (ii) Het is a 5- or 6-membered heteroaryl, R6 is —(CH2)1-2—, and R6 and Het together with the atoms to which they are attached form a 5,5-, 5,6-, 5,7-, 6,5-, 6,6- or 6,7-bicyclic ring system;
- R7 is —C(O)R17, —S(O)R18 or —SO2R18;
- R17 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, methylaminomethylalkenyl, dimethylaminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylalkynyl, aminomethylalkynyl, methylaminomethylalkynyl, dimethylaminomethylalkynyl, alkoxy, haloalkoxy, alkenyloxy, alkynyloxy, —NH—(CH2)2—R19, —O—(CH2)2—R19 or —NR20R21;
- where R19 is —OR9 or —NR9R10, and R20 and R21 are each independently H, alkyl, cycloalkyl or haloalkyl;
- and
- R18 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylalkynyl, aminomethylalkynyl, or —NR9R10.
29 more elements
A compound of Formula I:
- or a pharmaceutically acceptable derivative thereof, wherein:
- a is 0-2;
- R1 is H, alkyl, haloalkyl or halo;
- R2 is alkyl, cycloalkyl or haloalkyl;
- R3 is —O—(CH2)b—R8;
- b is 1-4;
- R8 is H, CN, OH, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, NR9R10, C(O)R11, C(═NH)(R12) or C(═N—O—R9)(R12);
- R9 and R10 are each independently H, alkyl or C(O)R13;
- where R13 is alkyl, alkoxy or NR14R15;
- R11 is hydroxy, alkyl, alkoxy or NR14R15;
- R12 is alkyl or NR14R15;
- R14 and R15 are each independently H, OH, alkoxy or alkyl, or together with the nitrogen atom to which they are attached form heterocyclyl;
- R4 is H or alkoxy;
- Z1, Z2 and Z3 are selected from (i), (ii) or (iii):
- (i) Z1 is N, one of Z2 and Z3 is C and the other of Z2 and Z3 is N,
- (ii) Z1 is NH or O, and Z2 and Z3 are C, or
- (iii) Z1 is CH, one of Z2 and Z3 is C and the other of Z2 and Z3 is N;
- Z4, Z5 and Z6 are selected from (i), (ii), (iii) or (iv):
- (i) Z4 is N, Z5 is CR5, and Z6 is CH,
- (ii) Z4 is CR16, Z5 is N, and Z6 is CH,
- (iii) Z4 is CR16, Z5 is CR5, and Z6 is N, or
- (iv) Z4 is CR16, Z5 is CR5, and Z6 is CH;
- R5 and R16 are selected from (i) or (ii):
- (i) R5 and R16 are each independently H, cyano, halo, alkoxy, amino, alkylamino, dialkylamino, alkyl, alkenyl, alkynyl or haloalkyl, or
- (ii) R5 and R16 together form alkylene or heteroalkylene;
- X is CR22R23, where R22 and R23 are each independently H or alkyl;
- Het and R6 are selected from (i) or (ii):
- (i) Het is a 5- or 6-membered heteroaryl, and R6 is H, alkyl or haloalkyl, or
- (ii) Het is a 5- or 6-membered heteroaryl, R6 is —(CH2)1-2—, and R6 and Het together with the atoms to which they are attached form a 5,5-, 5,6-, 5,7-, 6,5-, 6,6- or 6,7-bicyclic ring system;
- R7 is —C(O)R17;
- and
- R17 is alkoxy, alkenyloxy, alkynyloxy or —O—(CH2)2—R19;
- where R19 is —OR9 or —NR9R10.
30 more elements
A compound of Formula II:
- or a pharmaceutically acceptable derivative thereof, wherein:
- a is 0-2;
- R1 and R2 together form alkylene;
- R3 is —O—(CH2)b—R8;
- b is 1-4;
- R8 is H, CN, OH, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, NR9R10, C(O)R11, C(═NH)(R12) or C(═N—O—R9)(R12);
- R9 and R10 are each independently H, alkyl or C(O)R13;
- where R13 is alkyl, alkoxy or NR14R15;
- R11 is hydroxy, alkyl, alkoxy or NR14R15;
- R12 is alkyl or NR14R15;
- R14 and R15 are each independently H, OH, alkoxy or alkyl, or together with the nitrogen atom to which they are attached form heterocyclyl;
- R4 is H or alkoxy;
- Z1, Z2 and Z3 are selected from (i), (ii) or (iii):
- (i) Z1 is N, one of Z2 and Z3 is C and the other of Z2 and Z3 is N,
- (ii) Z1 is NH or O, and Z2 and Z3 are C, or
- (iii) Z1 is CH, one of Z2 and Z3 is C and the other of Z2 and Z3 is N;
- Z4, Z5 and Z6 are selected from (i), (ii), (iii) or (iv):
- (i) Z4 is N, Z5 is CR5, and Z6 is CH,
- (ii) Z4 is CR16, Z5 is N, and Z6 is CH,
- (iii) Z4 is CR16, Z5 is CR5, and Z6 is N, or
- (iv) Z4 is CR16, Z5 is CR5, and Z6 is CH;
- R5 and R16 are selected from (i) or (ii):
- (i) R5 and R16 are each independently H, cyano, halo, alkoxy, amino, alkylamino, dialkylamino, alkyl, alkenyl, alkynyl or haloalkyl, or
- (ii) R5 and R16 together form alkylene or heteroalkylene;
- X is O, S(O)x or CH2, where x is 0-2;
- Het and R6 are selected from (i) or (ii):
- (i) Het is a 5- or 6-membered heteroaryl, and R6 is H, alkyl or haloalkyl, or
- (ii) Het is a 5- or 6-membered heteroaryl, R6 is —(CH2)1-2—, and R6 and Het together with the atoms to which they are attached form a 5,5-, 5,6-, 5,7-, 6,5-, 6,6- or 6,7-bicyclic ring system;
- R7 is —C(O)R17, —S(O)R18 or —SO2R18;
- R17 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, methylaminomethylalkenyl, dimethylaminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylalkynyl, aminomethylalkynyl, methylaminomethylalkynyl, dimethylaminomethylalkynyl, alkoxy, haloalkoxy, alkenyloxy, alkynyloxy, —NH—(CH2)2—R19, —O—(CH2)2—R19 or —NR20R21;
- where R19 is —OR9 or —NR9R10, and R20 and R21 are each independently H, alkyl, cycloalkyl or haloalkyl;
- and
- R18 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylalkynyl, aminomethylalkynyl, or —NR2OR21.
30 more elements
A compound of Formula II:
- or a pharmaceutically acceptable derivative thereof, wherein:
- a is 0-2;
- R1 and R2 are selected from (i) or (ii);
- (i) R1 is alkyl, cycloalkyl or haloalkyl;
- and R2 is H, alkyl, haloalkyl, alkoxy, cycloalkoxy, haloalkoxy or halo, or
- (ii) R1 and R2 together form alkylene;
- R3 is —O—(CH2)b—R8;
- b is 1-4;
- R8 is H, CN, OH, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, NR9R10, C(O)R11, C(═NH)(R12) or C(═N—O—R9)(R12);
- R9 and R10 are each independently H, alkyl or C(O)R13;
- where R13 is alkyl, alkoxy or NR14R15;
- R11 is hydroxy, alkyl, alkoxy or NR14R15;
- R12 is alkyl or NR14R15;
- R14 and R15 are each independently H, OH, alkoxy or alkyl, or together with the nitrogen atom to which they are attached form heterocyclyl;
- R4 is H or alkoxy;
- Z1, Z2 and Z3 are selected from (i), (ii) or (iii):
- (i) Z1 is N, one of Z2 and Z3 is C and the other of Z2 and Z3 is N,
- (ii) Z1 is NH or O, and Z2 and Z3 are C, or
- (iii) Z1 is CH, one of Z2 and Z3 is C and the other of Z2 and Z3 is N;
- Z4 is CR16;
- Z5 is CR5;
- Z6 is N or CH;
- R5 and R16 together form alkylene or heteroalkylene;
- X is O, S(O)x or CH2, where x is 0-2;
- Het and R6 are selected from (i) or (ii):
- (i) Het is a 5- or 6-membered heteroaryl, and R6 is H, alkyl or haloalkyl, or
- (ii) Het is a 5- or 6-membered heteroaryl, R6 is —(CH2)1-2—, and R6 and Het together with the atoms to which they are attached form a 5,5-, 5,6-, 5,7-, 6,5-, 6,6- or 6,7-bicyclic ring system;
- R7 is —C(O)R17, —S(O)R18 or —SO2R18;
- R17 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, methylaminomethylalkenyl, dimethylaminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylalkynyl, aminomethylalkynyl, methylaminomethylalkynyl, dimethylaminomethylalkynyl, alkoxy, haloalkoxy, alkenyloxy, alkynyloxy, —NH—(CH2)2—R19, —O—(CH2)2—R19 or —NR20R21;
- where R19 is —OR9 or —NR9R10, and R20 and R21 are each independently H, alkyl, cycloalkyl or haloalkyl;
- and
- R18 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylalkynyl, aminomethylalkynyl, or —NR9R10.
29 more elements
A compound of Formula II:
- or a pharmaceutically acceptable derivative thereof, wherein:
- a is 0-2;
- R1 and R2 are selected from (i) or (ii):
- (i) R1 is alkyl, cycloalkyl or haloalkyl, and R2 is H, alkyl, haloalkyl, alkoxy, cycloalkoxy, haloalkoxy or halo, or
- (ii) R1 and R2 together form alkylene;
- R3 is —O—(CH2)b—R8;
- b is 1-4;
- R8 is H, CN, OH, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, NR9R10, C(O)R11, C(═NH)(R12) or C(═N—O—R9)(R12);
- R9 and R10 are each independently H, alkyl or C(O)R13;
- where R13 is alkyl, alkoxy or NR14R15;
- R11 is hydroxy, alkyl, alkoxy or NR14R15;
- R12 is alkyl or NR14R15;
- R14 and R15 are each independently H, OH, alkoxy or alkyl, or together with the nitrogen atom to which they are attached form heterocyclyl;
- R4 is H or alkoxy;
- Z1, Z2 and Z3 are selected from (i), (ii) or (iii):
- (i) Z1 is N, one of Z2 and Z3 is C and the other of Z2 and Z3 is N,
- (ii) Z1 is NH or O, and Z2 and Z3 are C, or
- (iii) Z1 is CH, one of Z2 and Z3 is C and the other of Z2 and Z3 is N;
- Z4, Z5 and Z6 are selected from (i), (ii), (iii) or (iv):
- (i) Z4 is N, Z5 is CR5, and Z6 is CH,
- (ii) Z4 is CR16, Z5 is N, and Z6 is CH,
- (iii) Z4 is CR16, Z5 is CR5, and Z6 is N, or
- (iv) Z4 is CR16, Z5 is CR5, and Z6 is CH;
- R5 and R16 are selected from (i) or (ii):
- (i) R5 and R16 are each independently H, cyano, halo, alkoxy, amino, alkylamino, dialkylamino, alkyl, alkenyl, alkynyl or haloalkyl, or
- (ii) R5 and R16 together form alkylene or heteroalkylene;
- X is O or S(O)x, where x is 0-2;
- Het and R6 are selected from (i) or (ii):
- (i) Het is a 5- or 6-membered heteroaryl, and R6 is H, alkyl or haloalkyl, or
- (ii) Het is a 5- or 6-membered heteroaryl, R6 is —(CH2)1-2—, and R6 and Het together with the atoms to which they are attached form a 5,5-, 5,6-, 5,7-, 6,5-, 6,6- or 6,7-bicyclic ring system;
- R7 is —C(O)R17, —S(O)R18 or —SO2R18;
- R17 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, methylaminomethylalkenyl, dimethylaminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylalkynyl, aminomethylalkynyl, methylaminomethylalkynyl, dimethylaminomethylalkynyl, alkoxy, haloalkoxy, alkenyloxy, alkynyloxy, —NH—(CH2)2—R19, —O—(CH2)2—R19 or —NR20R21;
- where R19 is —OR9 or —NR9R10, and R20 and R21 are each independently H, alkyl, cycloalkyl or haloalkyl;
- and
- R18 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylalkynyl, aminomethylalkynyl, or —NR9R10.
32 more elements
A compound of Formula II:
- or a pharmaceutically acceptable derivative thereof, wherein:
- a is 0-2;
- R1 is alkyl, cycloalkyl or haloalkyl;
- R2 is H, alkyl, haloalkyl, alkoxy, cycloalkoxy, haloalkoxy or halo;
- R3 is —O—(CH2)b—R8;
- b is 1-4;
- R8 is H, CN, OH, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, NR9R10, C(O)R11, C(═NH)(R12) or C(═N—O—R9)(R12);
- R9 and R10 are each independently H, alkyl or C(O)R13;
- where R13 is alkyl, alkoxy or NR14R15;
- R11 is hydroxy, alkyl, alkoxy or NR14R15;
- R12 is alkyl or NR14R15;
- R14 and R15 are each independently H, OH, alkoxy or alkyl, or together with the nitrogen atom to which they are attached form heterocyclyl;
- R4 is H or alkoxy;
- Z1, Z2 and Z3 are selected from (i), (ii) or (iii):
- (i) Z1 is N, one of Z2 and Z3 is C and the other of Z2 and Z3 is N,
- (ii) Z1 is NH or O, and Z2 and Z3 are C, or
- (iii) Z1 is CH, one of Z2 and Z3 is C and the other of Z2 and Z3 is N;
- Z4, Z5 and Z6 are selected from (i), (ii), (iii) or (iv):
- (i) Z4 is N, Z5 is CR5, and Z6 is CH,
- (ii) Z4 is CR16, Z5 is N, and Z6 is CH,
- (iii) Z4 is CR16, Z5 is CR5, and Z6 is N, or
- (iv) Z4 is CR16, Z5 is CR5, and Z6 is CH;
- R5 and R16 are selected from (i) or (ii):
- (i) R5 and R16 are each independently H, cyano, halo, alkoxy, amino, alkylamino, dialkylamino, alkyl, alkenyl, alkynyl or haloalkyl, or
- (ii) R5 and R16 together form alkylene or heteroalkylene;
- X is CR22R23, where R22 and R23 are each independently H or alkyl;
- Het and R6 are selected from (i) or (ii):
- (i) Het is a 5- or 6-membered heteroaryl, and R6 is H, alkyl or haloalkyl, or
- (ii) Het is a 5- or 6-membered heteroaryl, R6 is —(CH2)1-2—, and R6 and Het together with the atoms to which they are attached form a 5,5-, 5,6-, 5,7-, 6,5-, 6,6- or 6,7-bicyclic ring system;
- R7 is —C(O)R17;
- and
- R17 is alkoxy, alkenyloxy, alkynyloxy or —O—(CH2)2—R19;
- where R19 is —OR9 or —NR9R10.
30 more elements
A compound of Formula III:
- or a pharmaceutically acceptable derivative thereof, wherein:
- a is 0-2;
- R1 and R2 together form alkylene;
- R3 is —O—(CH2)b—R8;
- b is 1-4;
- R8 is H, CN, OH, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, NR9R10, C(O)R11, C(═NH)(R12) or C(═N—O—R9)(R12);
- R9 and R10 are each independently H, alkyl or C(O)R13;
- where R13 is alkyl, alkoxy or NR14R15;
- R11 is hydroxy, alkyl, alkoxy or NR14R15;
- R12 is alkyl or NR14R15;
- R14 and R15 are each independently H, OH, alkoxy or alkyl, or together with the nitrogen atom to which they are attached form heterocyclyl;
- R4 is H or alkoxy;
- Z1, Z2 and Z3 are selected from (i), (ii) or (iii):
- (i) Z1 is N, one of Z2 and Z3 is C and the other of Z2 and Z3 is N,
- (ii) Z1 is NH or O, and Z2 and Z3 are C, or
- (iii) Z1 is CH, one of Z2 and Z3 is C and the other of Z2 and Z3 is N;
- Z4, Z5 and Z6 are selected from (i), (ii), (iii) or (iv):
- (i) Z4 is N, Z5 is CR5, and Z6 is CH,
- (ii) Z4 is CR16, Z5 is N, and Z6 is CH,
- (iii) Z4 is CR16, Z5 is CR5, and Z6 is N, or
- (iv) Z4 is CR16, Z5 is CR5, and Z6 is CH;
- R5 and R16 are selected from (i) or (ii):
- (i) R5 and R16 are each independently H, cyano, halo, alkoxy, amino, alkylamino, dialkylamino, alkyl, alkenyl, alkynyl or haloalkyl, or
- (ii) R5 and R16 together form alkylene or heteroalkylene;
- X is O, S(O)x or CH2, where x is 0-2;
- Het and R6 are selected from (i) or (ii):
- (i) Het is a 5- or 6-membered heteroaryl, and R6 is H, alkyl or haloalkyl, or
- (ii) Het is a 5- or 6-membered heteroaryl, R6 is —(CH2)1-2—, and R6 and Het together with the atoms to which they are attached form a 5,5-, 5,6-, 5,7-, 6,5-, 6,6- or 6,7-bicyclic ring system;
- R7 is —C(O)R17, —S(O)R18 or —SO2R18;
- R17 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, methylaminomethylalkenyl, dimethylaminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylalkynyl, aminomethylalkynyl, methylaminomethylalkynyl, dimethylaminomethylalkynyl, alkoxy, haloalkoxy, alkenyloxy, alkynyloxy, —NH—(CH2)2—R19, —O—(CH2)2—R19 or —NR20R21;
- where R19 is —OR9 or —NR9R10, and R20 and R21 are each independently H, alkyl, cycloalkyl or haloalkyl;
- and
- R18 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylalkynyl, aminomethylalkynyl, or —NR2OR21.
30 more elements
A compound of Formula III:
- or a pharmaceutically acceptable derivative thereof, wherein:
- a is 0-2;
- R1 and R2 are selected from (i) or (ii):
- (i) R1 and R2 are each independently alkyl, cycloalkyl or haloalkyl, or
- (ii) R1 and R2 together form alkylene;
- R3 is —O—(CH2)b—R8;
- b is 1-4;
- R8 is H, CN, OH, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, NR9R10, C(O)R11, C(═NH)(R12) or C(═N—O—R9)(R12);
- R9 and R10 are each independently H, alkyl or C(O)R13;
- where R13 is alkyl, alkoxy or NR14R15;
- R11 is hydroxy, alkyl, alkoxy or NR14R15;
- R12 is alkyl or NR14R15;
- R14 and R15 are each independently H, OH, alkoxy or alkyl, or together with the nitrogen atom to which they are attached form heterocyclyl;
- R4 is H or alkoxy;
- Z1, Z2 and Z3 are selected from (i), (ii) or (iii):
- (i) Z1 is N, one of Z2 and Z3 is C and the other of Z2 and Z3 is N,
- (ii) Z1 is NH or O, and Z2 and Z3 are C, or
- (iii) Z1 is CH, one of Z2 and Z3 is C and the other of Z2 and Z3 is N;
- Z4 is CR16;
- Z5 is CR5;
- Z6 is N or CH;
- R5 and R16 together form alkylene or heteroalkylene;
- X is O, S(O)x or CH2, where x is 0-2;
- Het and R6 are selected from (i) or (ii):
- (i) Het is a 5- or 6-membered heteroaryl, and R6 is H, alkyl or haloalkyl, or
- (ii) Het is a 5- or 6-membered heteroaryl, R6 is —(CH2)1-2—, and R6 and Het together with the atoms to which they are attached form a 5,5-, 5,6-, 5,7-, 6,5-, 6,6- or 6,7-bicyclic ring system;
- R7 is —C(O)R17, —S(O)R18 or —SO2R18;
- R17 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, methylaminomethylalkenyl, dimethylaminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylalkynyl, aminomethylalkynyl, methylaminomethylalkynyl, dimethylaminomethylalkynyl, alkoxy, haloalkoxy, alkenyloxy, alkynyloxy, —NH—(CH2)2—R19, —O—(CH2)2—R19 or —NR20R21;
- where R19 is —OR9 or —NR9R10, and R20 and R21 are each independently H, alkyl, cycloalkyl or haloalkyl;
- and
- R18 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylalkynyl, aminomethylalkynyl, or —NR9R10.
28 more elements
A compound of Formula III:
- or a pharmaceutically acceptable derivative thereof, wherein:
- a is 0-2;
- R1 and R2 are selected from (i) or (ii):
- (i) R1 and R2 are each independently alkyl, cycloalkyl or haloalkyl, or
- (ii) R1 and R2 together form alkylene;
- R3 is —O—(CH2)b—R8;
- b is 1-4;
- R8 is H, CN, OH, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, NR9R10, C(O)R″, C(═NH)(R12) or C(═N—O—R9)(R12);
- R9 and R10 are each independently H, alkyl or C(O)R13;
- where R13 is alkyl, alkoxy or NR14R15;
- R11 is hydroxy, alkyl, alkoxy or NR14R15;
- R12 is alkyl or NR14R15;
- R14 and R15 are each independently H, OH, alkoxy or alkyl, or together with the nitrogen atom to which they are attached form heterocyclyl;
- R4 is H or alkoxy;
- Z1, Z2 and Z3 are selected from (i), (ii) or (iii):
- (i) Z1 is N, one of Z2 and Z3 is C and the other of Z2 and Z3 is N,
- (ii) Z1 is NH or O, and Z2 and Z3 are C, or
- (iii) Z1 is CH, one of Z2 and Z3 is C and the other of Z2 and Z3 is N;
- Z4, Z5 and Z6 are selected from (i), (ii), (iii) or (iv):
- (i) Z4 is N, Z5 is CR5, and Z6 is CH,
- (ii) Z4 is CR16, Z5 is N, and Z6 is CH,
- (iii) Z4 is CR16, Z5 is CR5, and Z6 is N, or
- (iv) Z4 is CR16, Z5 is CR5, and Z6 is CH;
- R5 and R16 are selected from (i) or (ii):
- (i) R5 and R16 are each independently H, cyano, halo, alkoxy, amino, alkylamino, dialkylamino, alkyl, alkenyl, alkynyl or haloalkyl, or
- (ii) R5 and R16 together form alkylene or heteroalkylene;
- X is O or S(O)x, where x is 0-2;
- Het and R6 are selected from (i) or (ii):
- (i) Het is a 5- or 6-membered heteroaryl, and R6 is H, alkyl or haloalkyl, or
- (ii) Het is a 5- or 6-membered heteroaryl, R6 is —(CH2)1-2—, and R6 and Het together with the atoms to which they are attached form a 5,5-, 5,6-, 5,7-, 6,5-, 6,6- or 6,7-bicyclic ring system;
- R7 is —C(O)R17, —S(O)R18 or —SO2R18;
- R17 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, methylaminomethylalkenyl, dimethylaminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylalkynyl, aminomethylalkynyl, methylaminomethylalkynyl, dimethylaminomethylalkynyl, alkoxy, haloalkoxy, alkenyloxy, alkynyloxy, —NH—(CH2)2—R19, —O—(CH2)2—R19 or —NR20R21;
- where R19 is —OR9 or —NR9R10, and R20 and R21 are each independently H, alkyl, cycloalkyl or haloalkyl;
- and
- R18 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylalkynyl, aminomethylalkynyl, or —NR9R10.
32 more elements
Dependencies are inferred from the claim text.